1. PTSD Treatment: The State of the Evidence Paula P. Schnurr, Ph.D VA National Center for PTSD, Executive Division Dartmouth Medical School

2. Overview Review evidence on the treatment of PTSD Describe the new VA/DoD Practice Guideline for PTSD Discuss implications for treating women veterans

3. Medication.36 N = 51 Anti- depressant.40 N = 30 Atyp. Anti- psychotic.39 N = 8 Somatic 1.15 N = 4 Acu- puncture 1.28 N = 1 Psychotherapy 1.13 N = 67 CBT 1.26 N = 47 EMDR 1.04 N = 10 Group.46 N = 6 Other -.53-.78 N = 4 (some ns) Effectiveness of Treatments for PTSD Only significant 1 st and 2 nd level categories are shown. – Watts, Schnurr et al., under review. Effect sizes are represented as a modified Hedges g, indicating benefit relative to a control group. N = number of comparisons.

4. Meta-Regression of Psychotherapy and Medication Effects PsychotherapyMedication Effect size1.13.36** Adjusted effect size a.91.41* a Adjusted for type of comparison group, missing data procedure, blinding, % of veteran subjects, and % of women. *p<.05, **p<.001 – Watts, Schnurr et al., under review. Effect sizes are represented as a modified Hedges g, indicating benefit relative to a control group.

5. Effect Sizes for Types of Medication N Anti- depressants Effect size (95% CI) N Atypical Anti- psychotics Effect size (95% CI) 18SSRIs.42 (.26-.58)6Risperidone.50 (.12-.87) 2Venlafaxine.48 (.33-.63)2Olanzapine -.10 (-1.52- 1.31) 3Tricyclics.36 (-.01-.73) 4MAOIs.28 (-.10-.65) 3Other ADs.14 (-.28-.55) – Watts, Schnurr et al., under review. Effect sizes are represented as a modified Hedges g, indicating benefit relative to a control group.

6. Effect Sizes for Eye Movement Desensitization & Reprocessing for PTSD –Chemtob et al., 2000, from ISTSS Practice Guideline

7. Effect Sizes for Types of Cognitive-Behavioral Therapy Primarily Cognitive Primarily Exposur e Cognitive & Exposure Stress Inoculation Effect size 1.711.091.311.37 95% CI1.21.2.12.86-1.33.93-1.69.80-1.94 % waitlist control 71%48%72%100% All comparisons between treatments are not statistically significant – Watts, Schnurr et al., under review. Effect sizes are represented as a modified Hedges g, indicating benefit relative to a control group.

8. Effect Sizes for Psychotherapy & Medication by Percentage of Veteran Subjects NPsychotherapyNMedication 0%531.26 (1.09-1.43)10.43 (.19-.69)** 1-20%31.09 (.70-1.50)17.49 (.42-.56)* 21-99%0—5.19 (.00-.45) 100%12.46 (.11-.81)19.30 (.09-.52) Psychotherapy > medication: *p<.05, **p<.001 – Watts, Schnurr et al., under review. Effect sizes are represented as a modified Hedges g, indicating benefit relative to a control group.

9. VA/DoD Clinical Practice Guideline for Management of Post-Traumatic Stress Update–2010 www.healthquality.va.gov www.qmo.amedd.army.mil

10. Why Have Clinical Practice Guidelines? To inform practice To enhance patient outcomes To reduce unnecessary variation To promote efficient and effective use of resources

11. Methods of Guideline Development Based on systematic reviews and meta- analyses of evidence Guidelines vary in what is considered and how evidence is weighted -Well-done randomized controlled trials carry the highest weight -Other studies may be considered -Quality and amount of evidence is considered

12. VA/DoD Guideline Content Module A:Acute stress reaction, early interventions, preventing PTSD Module B:Treatment of PTSD, management of specific symptoms Event 4 days 1 month 3 months ASR ASD | Acute PTSD Chronic PTSD Module A | Module B – Adapted from M.J. Friedman

13. Differences From the 2004 VA/DoD Guideline Original 5 modules have been consolidated into 2 modules: 1.Acute Stress Response and early prevention of PTSD 2.Treatment of PTSD Guideline recommendations are patient- centered, regardless of setting of care Psychological First Aid – Key concept as initial response – Adapted from M.J. Friedman

14. More Differences From the 2004 VA/DoD Guideline Pharmacotherapy for prevention is now not recommended -Brief psychotherapy for symptomatic (> 2 weeks) trauma survivors is recommended Stronger evidence for 1st line treatments: -Psychotherapy CBT (ET, CT, --SIT, EMDR) -Pharmacotherapy (SSRI/SNRI) Inclusion of CAM: acupuncture Recommendations to address specific symptoms of insomnia, pain and anger – Adapted from M.J. Friedman

15. Strength of Recommendations A strong recommendation that clinicians provide the intervention to eligible patients. Good evidence … that the intervention improves important health outcomes and … benefits substantially outweigh harm. A A recommendation that clinicians provide (the service) to eligible patients. At least fair evidence … that the intervention improves health outcomes and … benefits outweigh harm. B No recommendation for or against the routine provision of the intervention is made. At least fair evidence … that the intervention can improve health outcomes but … the balance of benefits and harms is too close to justify a general recommendation. C …evidence is insufficient to recommend for or against routinely providing the intervention. Evidence that the intervention is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms can not be determined. I

16. VA/DoD Practice Guideline: Psychotherapy Recommendations Balance = Benefit - Harm SRSUBSTANTIALSOMEWHATUNKNOWN ATrauma-focused psychotherapy that includes components of exposure and/or cognitive restructuring; OR Stress inoculation training CPatient Education, Imagery Rehearsal Therapy, Psychodynamic Therapy, Hypnosis, Relaxation Techniques, Group Therapy I Family therapyWeb-Based CBT, Dialectical Behavior Therapy, Acceptance & Commitment Therapy SR = Strength of recommendation (Full Guideline, p. 115).

17. Level A Psychotherapy Choices Patients should be offered one of the evidence-based trauma-focused psychotherapeutic interventions that include components of exposure and/or cognitive restructuring; OR stress inoculation training. [A] Choice should be based on symptom severity, clinician expertise, and patient preference, and may include: -Exposure therapy (e.g., Prolonged Exposure) -Cognitive therapy (e.g., Cognitive Processing Therapy) -Stress management therapy (e.g., SIT) or -Eye Movement Desensitization & Reprocessing (EMDR)

18. Understanding the Evidence on Group-Based Treatment Recommendation for group: “Consider offering or providing” [Strength of recommendation: C] Findings do not favor trauma-focused vs. present- focused [Strength of recommendation: I] Analytic problems with current evidence -Influence of group members on each other can cause observations to be statistically nonindependent -Failing to address group clustering causes treatment effects to be overestimated

19. Effects of Corrected Analysis on Results of Group Treatment Baldwin et al. (2006) reanalysis of significant tests for evidence-based group treatments -Corrected dfs -Varied ICC assumptions Implications: evidence is optimistically biased

20. VA/DoD Practice Guideline: Pharmcotherapy Recommendations Balance = Benefit - Harm SR SUBSTANTIALSOMEWHATUNKNOWNNONE or HARM ASSRIs, SNRIs B Mirtazapine, Atypical AP (adjunct), TCAs, MAOIs (phenelzine), Prazosin (sleep), Nefazodone (caution) C Prazosin (PTSD) D Guanfacine, Topiramate, Valproate, Tiagabine Benzodiazepines (harm) I Buspirone, Bupropion, Non-benzo hypnotics, Lamotrigine, Clonidine, Gabapentin, Trazodone (adjunct), Atypical anti- psychotics (mono), Conventional anti- psychotics, Propranolol SR = Strength of recommendation (Full Guideline, p. 149).

21. Pharmacotherapy Choices As monotherapy, strongly recommend [A]: -SSRIs (fluoxetine, paroxetine, and sertraline have strongest support) -SNRIs (venlafaxine has the strongest support for treatment of PTSD) As adjunctive therapy, recommend [B]: -Atypical antipsychotics (risperidone and olanzapine) – Adapted from M.J. Friedman

22. VA/DoD Guideline: Therapy Selection Explain the range of available and effective therapeutic options for PTSD to all patients with PTSD Patient education is recommended as an element of treatment of PTSD for all patients and family members [C] Patient and provider preferences should drive the selection of evidence-based psychotherapy and/or evidence-based pharmacotherapy as 1 st line treatment Psychotherapies should be provided by practitioners who have been trained in that particular method A collaborative care approach to therapy administration, with care management, may be considered

23. In FY 2010, 5.9% of VA users were women Overall, 10.9% of women had PTSD vs. 8.2% of men Among OEF/OIF Veterans, 17.3% of women had PTSD vs. 23.6% of men

24. The Percentage of Veterans Who are Women is Growing – National Center for Veterans Analysis and Statistics, 2010

25. Women Who Use VA have Poorer Health Relative to Women in the General Population – Frayne et al., J Gen Intern Med 21:S40 (2006)  Veterans  General population Mental Health Subscales

26. Among VA Users, Women are More Likely Than Men to have Mental Health Problems From Frayne, VA Women’s Health Evaluation Initiative. Percents are based on presence of at least 2 instances of mental health condition ICD-9 codes in VA outpatient administrative data in FY08; includes veteran patients only. 26 31% of women vs. 20% of men have a diagnosed mental health condition

27. Among VA Users, Women are More Likely Than Men to have Military Sexual Trauma VA Users Screened for MST MenWomen Veterans Screened FY 2005 (N = 3,045,000) 1.1%21.8% OEF/OIF Veterans Screened FY 2001-2007 (N = 126,729) 0.7%15.1% – Kimerling et al., 2007 & in press

28. Implications of Findings for Treating PTSD in Women Veterans Sexual trauma is likely to be a focus -e.g., in CSP #494 (Prolonged Exposure), 70% identified it as their index trauma -Warzone trauma more common in OEF/OIF Little investigation of whether gender affects treatment response -No conclusive evidence to date Some women prefer gender-specific treatment in women’s clinics & groups

29. Future Directions How do we maximize efficiency? -e.g., using D-cycloserine to boost the effectiveness of exposure therapy How do we enhance access? -e.g., using telehealth What works for whom? -e.g., using comparative effectiveness research to identify optimal strategies for individual patients